Submissions for variant NM_058216.3(RAD51C):c.890_899del (p.Leu297fs)

dbSNP: rs1555602141

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000569137	SCV000671900	pathogenic	Hereditary cancer-predisposing syndrome	2023-05-03	criteria provided, single submitter	clinical testing	The c.890_899del10 pathogenic mutation, located in coding exon 6 of the RAD51C gene, results from a deletion of 10 nucleotides at nucleotide positions 890 to 899, causing a translational frameshift with a predicted alternate stop codon (p.L297Hfs*2). This alteration has been identified in a cohort of 2649 consecutive cases of breast and/or ovarian cancer and in an individual diagnosed with prostate cancer (Golmard L et al. Eur. J. Hum. Genet., 2017 12;25:1345-1353; Paulo P et al. PLoS Genet., 2018 04;14:e1007355). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000576176	SCV000676964	pathogenic	Fanconi anemia complementation group O	2024-11-13	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Leu297Hisfs*2) in the RAD51C gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RAD51C are known to be pathogenic (PMID: 20400964, 21990120, 24800917, 29278735). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with ovarian cancer (PMID: 25980754, 29255180, 29659569). ClinVar contains an entry for this variant (Variation ID: 484744). Studies have shown that this premature translational stop signal is associated with inconclusive levels of altered splicing (internal data). For these reasons, this variant has been classified as Pathogenic.
Mendelics	RCV000576176	SCV001140726	pathogenic	Fanconi anemia complementation group O	2019-05-28	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000569137	SCV001347925	pathogenic	Hereditary cancer-predisposing syndrome	2023-10-01	criteria provided, single submitter	clinical testing	This variant deletes 10 nucleotides in exon 6 of the RAD51C gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in one individual each affected with ovarian cancer (PMID: 29255180), breast and ovarian cancer (PMID: 33326660), bladder and prostate cancer (PMID: 29659569) and an individual affected with Lynch syndrome-associated cancer and/or polyps (PMID: 25980754). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of RAD51C function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Molecular Oncology Research Center, Barretos Cancer Hospital	RCV000709516	SCV001438607	pathogenic	Hereditary breast ovarian cancer syndrome	2020-08-01	criteria provided, single submitter	research
Sema4, Sema4	RCV000569137	SCV002530028	pathogenic	Hereditary cancer-predisposing syndrome	2021-12-20	criteria provided, single submitter	curation
GeneDx	RCV003314621	SCV004014214	pathogenic	not provided	2023-06-16	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25980754, Monteiro2019[MtgAbstract], 29659569, Cardoso2018[Thesis], 27535533, Teixeira2023[preprint], 33258288, 35264596, 33326660, 29255180, 36119527)
Baylor Genetics	RCV003459371	SCV004208015	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 3	2024-03-22	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV003459371	SCV004933029	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 3	2024-01-03	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.